Ghosh Soma, Chakraborty Arijit, Das Neelotpal, Bhowmick Subhamoy, Majumdar Kunal Kanti, Bhattacharjee Samsiddhi, Mukherjee Mouli, Sikdar Nilabja, Pramanik Sreemanta
Kolkata Zonal Centre, CSIR-National Environmental Engineering Research Institute, i-8 Sector-C, East Kolkata Township, Kolkata, 700107, India.
Dept. of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, 700126, West Bengal, India.
Biol Trace Elem Res. 2025 Jan 20. doi: 10.1007/s12011-025-04515-2.
AS3MT, GSTO2, and GSTP1 genes play important roles in the arsenic biotransformation pathway, while CYP2E1 gene has a prominent role in the metabolic activation of xenobiotics. Hence, polymorphisms of these genes might have an effect on arsenic biotransformation and could impact susceptibility to arsenical skin lesions in individuals of chronic arsenic toxicity. The present case-control study, comprising 148 subjects, attempted to evaluate genetic association between nine polymorphisms of AS3MT, GSTO2, GSTP1 and CYP2E1 genes and arsenical skin lesions in a West Bengal (WB) population. A statistically significant association was found between rs11191439 (AS3MT) and arsenical skin lesions (OR = 5.50, P-value = 0.01) using logistic regression with age and gender as covariates. Among non-genetic risk factors, age and groundwater arsenic were found to be significantly associated with skin lesions (P-value < 0.05). When haplotypes among the intragenic polymorphisms of AS3MT, CYP2E1 and GSTO2 genes were analyzed, 'ATA' and 'ACG' haplotypes of the AS3MT gene showed significant difference between the case and control. Multifactor dimensionality reduction (MDR) analysis was performed on the nine polymorphisms and groundwater and urinary arsenic for studying gene-environment interactions. Strong association was observed between groundwater arsenic and skin lesions relative to the SNPs (P-value < 10). The best model with maximum testing accuracy included one SNP from the AS3MT (rs11191439) and groundwater arsenic (P-value < 0.0001). The present study documents the first report about the association of AS3MT gene variant with skin lesions in an arsenic exposed population of WB. Presumably, this is also the first study that has used MDR to investigate gene-environment interactions in arsenic-induced toxicity.
AS3MT、GSTO2和GSTP1基因在砷生物转化途径中发挥重要作用，而CYP2E1基因在异源生物代谢激活中起显著作用。因此，这些基因的多态性可能影响砷的生物转化，并可能影响慢性砷中毒个体对砷性皮肤病变的易感性。本病例对照研究纳入了148名受试者，试图评估AS3MT、GSTO2、GSTP1和CYP2E1基因的9种多态性与西孟加拉邦（WB）人群砷性皮肤病变之间的遗传关联。以年龄和性别作为协变量进行逻辑回归分析，发现rs11191439（AS3MT）与砷性皮肤病变之间存在统计学显著关联（OR = 5.50，P值 = 0.01）。在非遗传风险因素中，发现年龄和地下水砷含量与皮肤病变显著相关（P值 < 0.05）。对AS3MT、CYP2E1和GSTO2基因的基因内多态性单倍型进行分析时，AS3MT基因的“ATA”和“ACG”单倍型在病例组和对照组之间存在显著差异。对这9种多态性以及地下水和尿砷进行多因素降维（MDR）分析，以研究基因-环境相互作用。相对于单核苷酸多态性（SNP），观察到地下水砷与皮肤病变之间存在强关联（P值 < 10）。具有最高测试准确性的最佳模型包括来自AS3MT的一个SNP（rs11191439）和地下水砷（P值 < 0.0001）。本研究记录了关于WB砷暴露人群中AS3MT基因变异与皮肤病变关联的首份报告。据推测，这也是首次使用MDR研究砷诱导毒性中基因-环境相互作用的研究。
